A NOVEL C.954G>T CHANGE (P.TRP318CYS) IN KLF1 GENE RESULTING IN AN IN(LU) PHENOTYPE

Abstract

Background: Luaand Lubare inherited as codominant allelic characters resulting from a single nucleotide variant (SNV) of the basal cell adhesion molecule (BCAM ) gene. Red cells of the dominantly inherited suppressor of the Lutheran antigens In(Lu) phenotypically appear as Lu(a–b–) by hemagglutination and can result from heterozygosity for variants within the erythroid-specific Krüppel-like factor 1 (KLF1 ) gene, an integral transcriptional activator for erythropoiesis. We investigated a sample from a 81-year old Caucasian Brazilian female patient with discrepant Lua and Lub RBC phenotyping and genotyping testing. Methods: Serologic testing was performed by hemmagglutination in gel using specific cards (BioRad, Cressier, Switzerland) and molecular testing was performed by HEA BeadChip (Immucor, Warren, NJ). Because of the discrepant serology and HEA for Lua and Lub phenotypes, Sanger sequencing of BCAM and KLF1 was also performed. Results: The patient RBCs typed Lu(a–b–) and HEA predicted a Lu(a+b+) phenotype. Genomic sequencing of BCAM showed the patient was heterozygous c.230G/A consistent with LU*A/LU*B genotype and revealed the common polymorphism c.586G/A (rs28399654) that does not impact the expression of Lutheran antigens. In KLF1 the novel c.954G>T in exon 3 encoding p.Trp318Cys was found. The change c.954G>C encoding the same amino acid change was previously reported associated with the In(Lu) phenotype and this allele has been assigned KLF*BGM62 by ISBT. Conclusion: Recognizing In(Lu) patients is important to provide better classification of KLF1 variants affecting Lutheran antigens expression and allow for phenotype prediction from genotype, accurate typing, and better transfusion management of related challenging transfusion scenarios.